Truqap Drug Interactions

Capivasertib is primarily metabolised by CYP3A4 and UGT2B7 enzymes. In vivo, capivasertib is a weak, time-dependent inhibitor of CYP3A.
Medicinal products that may increase capivasertib plasma concentrations: Strong CYP3A4 inhibitors: Co-administration of TRUQAP with strong CYP3A4 inhibitors increases capivasertib concentration, which may increase the risk of TRUQAP toxicity. Co-administration with strong CYP3A4 inhibitors should be avoided (e.g. boceprevir, ceritinib, clarithromycin, cobicistat, conivaptan, ensitrelvir, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, lonafarnib, mibefradil, mifepristone, nefazodone, nelfinavir, posaconazole, ribociclib, ritonavir, saquinavir, telaprevir, telithromycin, troleandomycin, tucatinib, voriconazole, grapefruit or grapefruit juice). If co-administration cannot be avoided, TRUQAP dose should be reduced (see Dosage & Administration). Co-administration of multiple 200 mg doses of the strong CYP3A4 inhibitor itraconazole increased capivasertib total exposure (AUC_inf) and the peak concentration (C_max) by 95% and 70%, respectively, relative to capivasertib given alone.
Moderate CYP3A4 inhibitors: Co-administration of TRUQAP with moderate CYP3A4 inhibitors increases capivasertib concentration, which may increase the risk of TRUQAP toxicity. TRUQAP dose should be reduced when co-administered with moderate CYP3A4 inhibitor (e.g aprepitant, ciprofloxacin, cyclosporine, diltiazem, erythromycin, fluconazole, fluvoxamine, tofisopam, verapamil) (see Dosage & Administration).
Medicinal products that may decrease capivasertib plasma concentrations: Strong CYP3A4 inducers: Co-administration of TRUQAP with strong CYP3A4 inducers (e.g. carbamazepine, phenytoin, rifampicin, St. John's wort) should be avoided. Co-administration of capivasertib with strong CYP3A4 inducer enzalutamide decreased the capivasertib AUC by approximately 40% to 50%.
Moderate CYP3A4 inducers: Co-administration of capivasertib with moderate CYP3A4 inducer has the potential to decrease the concentration of capivasertib. This may reduce the efficacy of TRUQAP. Co-administration of moderate CYP3A4 inducers should be avoided (e.g. bosentan, cenobamate, dabrafenib, elagolix, etravirine, lersivirine, lesinurad, lopinavir, lorlatinib, metamizole, mitapivat, modafinil, nafcillin, pexidartinib, phenobarbital, rifabutin, semagacestat, sotorasib, talviraline, telotristat ethyl, thioridazine).
Medicinal products whose plasma concentrations may be altered by capivasertib: Substrates of CYP3A: Concentration of medicinal products that are primarily eliminated via CYP3A metabolism may increase when co-administered with TRUQAP which may then lead to increased toxicity depending on their therapeutic window. Capivasertib increased the midazolam AUC by 15% to 77% and is therefore a weak CYP3A inhibitor (see Pharmacology: Pharmacokinetics under Actions). Dose adjustment may be required for medicinal products that are primarily eliminated via CYP3A metabolism and have narrow therapeutic window (e.g. carbamazepine, cyclosporine, fentanyl, pimozide, simvastatin, tacrolimus).The SmPC of the other medicinal products should be consulted for the recommendations regarding co-administration with weak CYP3A4 inhibitors.
CYP2D6 substrates with a narrow therapeutic index: In vitro evaluations indicated that capivasertib has a potential to inhibit the activities of CYP2D6 enzymes. Capivasertib should be used with caution in combination with sensitive substrates of CYP2D6 enzymes which exhibit a narrow therapeutic index because capivasertib may increase the systemic exposure of these substrates.
CYP2B6 substrates with a narrow therapeutic index: In vitro evaluations indicated that capivasertib has a potential to induce the activities of CYP2B6 enzymes. Capivasertib should be used with caution in combination with sensitive substrates of CYP2B6 enzymes which exhibit a narrow therapeutic index (e.g. bupropion) because capivasertib may decrease the systemic exposure of these substrates.
UGT1A1 substrates with a narrow therapeutic index: In vitro evaluations indicated that capivasertib has a potential to inhibit the activities of UGT1A1 enzymes. Capivasertib should be used with caution in combination with sensitive substrates of UGT1A1 enzymes which exhibit a narrow therapeutic index (e.g. irinotecan) because capivasertib may increase the systemic exposure of these substrates.
Interactions with hepatic transporters (BCRP, OATP1B1, OATP1B3): The exposure of medicinal products that are sensitive to inhibition of BCRP, OATP1B1 and/or OATP1B3, if they are metabolised by CYP3A4, may increase by co-administration with TRUQAP. This may lead to increased toxicity. Depending on their therapeutic window, dose adjustment may be required for medicinal products that are sensitive to inhibition of BCRP, OATP1B1 and/or OATP1B3 if they are metabolised by CYP3A4 (e.g. simvastatin). The SmPC of the other medicinal products should be consulted for the recommendations regarding co-administration with CYP3A4, BCRP, OATP1B1 and OATP1B3 inhibitors.
Interactions with renal transporters (MATE1, MATE2K, OCT2): The exposure of medicinal products that are sensitive to inhibition of MATE1, MATE2K and/or OCT2 may increase by co-administration with TRUQAP. This may lead to increased toxicity. Depending on their therapeutic window, dose adjustment may be needed for medicinal products that are sensitive to inhibition of MATE1, MATE2K and OCT2 (e.g. dofetilide, procainamide). The SmPC of the other medicinal products should be consulted for the recommendations regarding co-administration with MATE1, MATE2K and/or OCT2 inhibitors. Transient serum creatinine increases may be observed during treatment with TRUQAP due to inhibition of OCT2, MATE1 and MATE2K by capivasertib.